The tongue is critical for normal oromotor function in humans, yet we have only a limited understanding of human tongue neuromuscular organization and the bases for decline of tongue function with aging. Development of interventions for tongue dysfunction (e.g., strengthening of tongue muscles to prevent dysphagia) are hindered because the anatomical, molecular and physiological targets of these interventions are not known. The long term goals of this study are to determine the neuromuscular organization of key functional elements of the human tongue muscle system and how these elements change with development and aging to thereby improve clinical treatments for recovery of tongue dysfunction. To achieve these goals, this study applies anatomical, genetic, immunohistochemical, molecular and physiological techniques to the study of the adult and aged tongue in humans, macaques and rats. The results of these studies will meet three general aims. First, the architecture of tongue muscles will be studied to determine the structural bases of tongue movement diversity. Second, the molecular composition of tongue muscles will be studied to determine muscle phenotype and the extent of novel molecular expression in human tongue muscles. Third, the anatomical, physiological and molecular organization of muscles in the aged tongue will be studied to identify biological bases of age-related tongue dysfunction. These studies will provide important information on the neurobiology of the primate tongue and will provide the first direct tests of molecular bases of aging of the human tongue motor system. PUBLIC HEALTH RELEVANCE The objectives of this project are to determine the anatomical and molecular organization of human tongue muscles and to test for morphological and molecular correlates of tongue muscle dysfunction with aging.